Abstract
An adverse environmental experience of the growing fetus leads to permanent changes in the structure and contractile function of the heart; however, the mechanisms are incompletely understood. To examine if a maternal low protein (LP) diet can modulate the gene and protein expression of the Ca2+-cycling proteins in the neonatal heart, we employed a rat model in which pregnant dams were fed diets containing either 180 (normal) or 90 g (low) casein/kg diet for 2 weeks before mating and throughout pregnancy. A significant reduction in the L-type Ca2+-channel mRNA level in the LP group was detected at 1, 7, and 14 days of age. Although ryanodine receptor (RyR) mRNA levels progressively declined in the aging heart in both groups, the RyR mRNA levels were consistently higher in the LP group. A reduction in RyR protein content was seen only in the hearts of the LP group at 7 days of age. The Na+-Ca2+-exchanger (NCX) mRNA level was also markedly increased at all ages. Although an increase in sarco(endo)plasmic reticulum ATPase 2a (SERCA) 2a mRNA was only detected in the LP group at 7 days of age, corresponding protein level was depressed. On the other hand, an initial decrease (at 1 day of age) followed by an increase (at 14 and 28 days of age) in phospholamban (PLB) mRNA levels was detected. Although PLB protein level was also depressed at 1 day of age in the LP group, a marked increase was seen at 7 days of age. Moreover, the ratio of serine 16 and threonine 17 phosphorylated PLB to non-phosphorylated PLB was reduced at 7 days of age in the hearts of offspring of the LP group. These data suggest that maternal LP diet can induce alterations in the gene expression and protein levels of the Ca2+-cycling proteins in the neonatal heart.
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References
Tappia PS, Gabriel CA (2006) Role of nutrition in the development of the fetal cardiovascular system. Expert Rev Cardiovasc Ther 4:211–225. doi:10.1586/14779072.4.2.211
Cheema KK, Dent MR, Aroutiounova N, Tappia PS (2005) Prenatal exposure to maternal undernutrition induces adult cardiac dysfunction. Br J Nutr 93:471–477. doi:10.1079/BJN20041392
Tappia PS, Nijjar MS, Mahay A, Aroutiounova N, Dhalla NS (2005) Phospholipid profile in developing heart of rats exposed to low protein diet in pregnancy. Am J Physiol 289:R1400–R1406
Aroutiounova N, Fandrich R, Kardami E, Tappia PS (2007) Prenatal exposure to maternal low protein is accompanied by altered cell mitotic index in the postnatal heart. J Mol Cell Cardiol 42:S87. doi:10.1016/j.yjmcc.2007.03.760
Diaz ME, Graham HK, O’Neill SC, Trafford AW, Eisner DA (2005) The control of sarcoplasmic reticulum Ca content in cardiac muscle. Cell Calcium 38:391–396. doi:10.1016/j.ceca.2005.06.017
Dhalla NS, Pierce GN, Panagia V, Singal PK, Beamish RE (1982) Calcium movements in relation to heart function. Basic Res Cardiol 77:117–139. doi:10.1007/BF01908167
Dhalla NS, Temsah RM, Netticadan T (2000) Role of oxidative stress in cardiovascular diseases. J Hypertens 18:655–673. doi:10.1097/00004872-200018060-00002
Dhalla NS, Afzal N, Beamish RE, Naimark B, Takeda N, Nagano M (1993) Pathophysiology of cardiac dysfunction in congestive heart failure. Can J Cardiol 9:873–887
Temsah RM, Netticadan T, Chapman D, Takeda S, Mochizuki S, Dhalla NS (1999) Alterations in sarcoplasmic reticulum function and gene expression in ischemic-reperfused rat heart. Am J Physiol 277:H584–H594
Shao Q, Ren B, Elimban V, Tappia PS, Takeda N, Dhalla NS (2005) Modification of sarcolemmal Na+-K+-ATPase and Na+/Ca2+ exchanger expression in heart failure by blockade of renin-angiotensin system. Am J Physiol Heart Circ Physiol 288:H2637–H2646. doi:10.1152/ajpheart.01304.2004
Saini HK, Shao Q, Musat S, Takeda N, Tappia PS, Dhalla NS (2005) Imidapril treatment improves the attenuated inotropic and intracellular calcium responses to ATP in heart failure due to myocardial infarction. Br J Pharmacol 144:202–211. doi:10.1038/sj.bjp.0705867
Netticadan T, Temsah RM, Kent A, Elimban V, Dhalla NS (2001) Depressed levels of Ca2+-cycling proteins may underlie sarcoplasmic reticulum dysfunction in the diabetic heart. Diabetes 50:2133–2138. doi:10.2337/diabetes.50.9.2133
Tappia PS, Dent MR, Aroutiounova N, Babick A, Weiler HA (2007) Gender differences in the modulation of cardiac gene expression by dietary conjugated linoleic acid isomers. Can J Physiol Pharmacol 85:465–475. doi:10.1139/Y06-104
Babick AP, Cantor EJF, Babick JT, Takeda N, Dhalla NS, Netticadan T (2004) Cardiac contractile dysfunction in J2N-k cardiomyopathic hamsters is associated with impaired SR function and regulation. Am J Physiol Cell Physiol 287:C1202–C1208. doi:10.1152/ajpcell.00155.2004
Trafford AW, Diaz ME, Sibbring GC, Eisner DA (2000) Modulation of CICR has no maintained effect on systolic Ca2+: simultaneous measurements of sarcoplasmic reticulum and sarcolemmal Ca2+ fluxes in rat ventricular myocytes. J Physiol 522:259–270. doi:10.1111/j.1469-7793.2000.t01-2-00259.x
Periasamy M, Kalyanasundaram A (2007) SERCA pump isoforms: their role in calcium transport and disease. Muscle Nerve 35:430–442. doi:10.1002/mus.20745
Santonastasi M, Wehrens XH (2007) Ryanodine receptors as pharmacological targets for heart disease. Acta Pharmacol Sin 28:937–944. doi:10.1111/j.1745-7254.2007.00582.x
Yano M (2008) Ryanodine receptor as a new therapeutic target of heart failure and lethal arrhythmia. Circ J 72:509–514. doi:10.1253/circj.72.509
Lacampagne A, Fauconnier J, Richard S (2008) Ryanodine receptor and heart disease. Med Sci 24:399–405
Ochi R, Gupte SA (2007) Ryanodine receptor: a novel therapeutic target in heart disease. Recent Patents Cardiovasc Drug Discov 2:110–118
de Trad Hejase C (2005) Phopholamban, a predicted candidate for early cardiac problem detection using signal processing techniques. Conf Proc IEEE Eng Med Biol Soc 3:2683–2686
Fernandez-Twinn DS, Ekizoglou S, Wayman A, Petry CJ, Ozanne SE (2006) Maternal low protein diet programs cardiac β-adrenergic response and signaling in 3-mo-old offspring. Am J Physiol Regul Integr Comp Physiol 291:R429–R436. doi:10.1152/ajpregu.00608.2005
Kawamura M, Itoh H, Yura S, Mogami H, Suga S, Makino H et al (2007) Undernutrition in utero augments systolic blood pressure and cardiac remodeling in adult mouse offspring: possible involvement of local cardiac angiotensin system in development of origins of cardiovascular disease. Endocrinology 148:1218–1225. doi:10.1210/en.2006-0706
Lim K, Zimanyi MA, Black MJ (2006) Effect of maternal protein restriction in rats on cardiac fibrosis and capillarization in adulthood. Pediatr Res 60:83–87. doi:10.1203/01.pdr.0000220361.08181.c3
Tarry-Adkins JL, Martin-Gronert MS, Chen JH, Cripps RL, Ozanne SE (2008) Maternal diet influences DNA damage, aortic telomere length, oxidative stress, and antioxidant defense capacity in rats. FASEB J 22:2037–2044. doi:10.1096/fj.07-099523
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This work was supported by a grant from the Manitoba Medical Service Foundation. Infrastructural support was provided by the St. Boniface Hospital and Research Foundation.
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Tappia, P.S., Sandhu, H., Abbi, T. et al. Alterations in the expression of myocardial calcium cycling genes in rats fed a low protein diet in utero. Mol Cell Biochem 324, 93–99 (2009). https://doi.org/10.1007/s11010-008-9988-x
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DOI: https://doi.org/10.1007/s11010-008-9988-x